EFFECTS OF ANTI-HYPERTENSIVE DRUGS ON PRODUCTION OF SOLUBLE FMS-LIKE TYROSINE KINASE 1 AND SOLUBLE ENDOGLIN FROM HUMAN NORMAL AND PRE-ECLAMPTIC PLACENTAS IN VITRO

• 1 Increases in soluble fms‐like tyrosine kinase 1 (sFlt‐1) and soluble endoglin (sEng) contribute to the pathogenesis of pre‐eclampsia. Soluble Flt‐1 binds to circulating free vascular endothelial growth factor and placenta growth factor and this is associated with endothelial dysfunction. Soluble endoglin, a transforming growth factor (TGF)‐β coreceptor, was reported to synergize with sFlt‐1 to amplify endothelial dysfunction by inhibiting TGF‐β1‐mediated vasorelaxation.
• 2 The aim of the present study was to examine whether the antihypertensive drugs clonidine (0.08–1.3 µg/mL), diazoxide (25–300 µg/mL), frusemide (60–1000 µg/mL) and hydralazine (6.3–100 µg/mL) have any effect on placental production of sFlt‐1 and sEng in placentas from normal and pre‐eclamptic pregnancies.
• 3 Explants were taken from non‐laboured term placentas of normal pregnancy (n = 5) and women with pre‐eclampsia (n = 5). Villous explants were cultured with increasing doses of antihypertensive drugs. Placental sFlt‐1 and sEng production was examined using ELISA.
• 4 Baseline sFlt‐1 production was higher in placentas from women with pre‐eclampsia than from normal pregnancy (4.5 ± 1.4 vs 3.2 ± 0.6 ng/mg of total protein, respectively; P < 0.001), as was sEng production (9.0 ± 2.3 vs 4.1 ± 0.6 ng/mg of total protein, respectively; P < 0.001). With the exception of frusemide, none of the antihypertensive drugs tested had any effect on sFlt‐1 and sEng production from placental explants of normal pregnancy and women with pre‐eclampsia. Increasing frusemide concentrations were correlated with increased sEng production in normal pregnancy (P < 0.005).
• 5 In conclusion, placental sFlt‐1 and sEng production was higher in pre‐eclampsia and antihypertensive drugs had no effect on placental production of sFlt‐1 and sEng in vitro.